Chapter 4. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology

A genetic variant found only in people of African descent significantly increases a smoker’s preference for cigarettes containing menthol, a flavor additive. The variant of the MRGPRX4 gene is five to eight times more frequent among smokers who use menthol cigarettes than other smokers, according to an international group of researchers supported by the U.S. Food and Drug Administration and the National Institutes of Health. The multiethnic study is the first to look across all genes to identify genetic vulnerability to menthol cigarettes. The paper was published online in the journal PLOS Genetics (link is external) on Feb. 15.
Menthol provides a minty taste and a cooling or soothing sensation, and plays a particularly troubling role in U.S. cigarette smoking patterns. According to the FDA, nearly 20 million people in the United States smoke menthol cigarettes, which are particularly popular among African-American smokers and teen smokers. In the U.S., 86 percent of African-American smokers use menthol cigarettes, compared to less than 30 percent of smokers of European descent. In addition, menthol cigarettes may be harder to quit than other cigarettes.
Although not originally the focus of the study, researchers also uncovered clues as to how menthol may reduce the irritation and harshness of smoking cigarettes.
“This study sheds light on the molecular mechanisms of how menthol interacts with the body,” said Andrew Griffith, M.D., Ph.D., scientific director and acting deputy director of NIH’s National Institute on Deafness and Other Communications Disorders (NIDCD). “These results can help inform public health strategies to lower the rates of harmful cigarette smoking among groups particularly vulnerable to using menthol cigarettes.”

/ By Ronnie Cohen
Dr. Samir Grover was taken aback when, early in his gastroenterology career, he saw one physician speak two times and present contradictory conclusions about the same medication. Each time, the speaker presented identical data on a drug used to treat inflammatory bowel disease. First, he recommended the pharmaceutical. A week later, he deemed it ineffective. “How could this exact same data be spun in two very different ways?” asked Grover, a professor at the University of Toronto. One fact did change — the drug manufacturer that sponsored and paid for the lecture.
“Simply following clinical practice guidelines could lead doctors — even those who shun all industry gifts — to unwittingly dispense financially tainted medicine”
It’s no secret that drug makers pay doctors to hype their products to other doctors. But few outside the halls of hospitals witness physicians bending a single set of facts in opposing ways. After watching similar acts of statistical wizardry throughout his nine years of medical practice, Grover set out to investigate a more sweeping question about conflicts of interest. Do they infect clinical practice guidelines? Professional societies produce thousands of these documents every year. They steer the decisions of health care professionals and insurance companies about how to prevent and treat an ever-widening range of conditions — from diabetes, hypertension, and heart disease to arthritis, hepatitis, cancer, and depression.
Grover and his colleagues’ paper and a companion study recently published in JAMA Internal Medicine suggest that simply following clinical practice guidelines could lead doctors — even those who shun all industry gifts — to unwittingly dispense financially tainted medicine. More than half of the authors of guidelines examined in the two studies had financial conflicts of interest. In many cases, the doctors who wrote the guidelines were paid by the same companies that produced the drugs they recommended. In addition, a significant portion of the doctors who took pharmaceutical money failed to disclose the payments, many of which amounted to $10,000 or more.
Copyright 2019 Undark

/ By Jacob Appel
One of the most upsetting illnesses any psychiatrist encounters is Wernicke-Korsakoff Syndrome (WKS). Caused by a deficiency of thiamine (vitamin B1), it results in devastating impairment of muscle control and memory. Able-bodied men and women develop a severe and irreversible amnesia that wipes clean their pasts and prevents them from forming new memories. Those who survive — and many patients don’t — are often relegated to nursing homes. Yet the neurological damage WKS causes is only part of what makes it so upsetting to emergency room psychiatrists; after all, many neurological and psychiatric illnesses inflict irreversible cognitive harm. The tragedy of WKS is that, with appropriate public health measures, it could be easily prevented.
Historically, thiamine deficiency afflicted the indigent, prisoners of war, and societies with rice-based diets. Its most serious chronic manifestation, beriberi, can present in a “wet” form that results in cardiac overload and massive edema, or in a “dry” variant — of which WKS is a subset — that affects the peripheral nervous system, the brain, or both. In addition to amnesia, victims of WKS often display striking degrees of spontaneous confabulation, in which they volunteer personal stories that they believe to be true but are not. Prevalence rates for WKS at autopsy have been found to run as high as 2.8 percent in Australia, and between 0.1 to 2.2 percent in the U.S.
Copyright 2019 Undark

/ By Courtenay Harris Bond
When Anna Brennan was 15 years old, her mother abandoned her in the projects of northeast Philadelphia. Her aunt eventually took her in, but Brennan struggled with anxiety and depression. She also needed to support herself, so in ninth grade she dropped out of high school and went to work at an all-night diner downtown. At 20, she met her first husband, who also lived with mental illness and had substance use issues — and gave her a tooth-marked scar in her upper right shoulder. For years, Brennan waitressed seven days a week until she had her third child, Gemma, and her back pain started, forcing her to quit.
“Our approach is: ‘Your urine is positive for substances. Let’s figure out how to make this work better for you.’”
A physician prescribed painkillers, and Brennan became addicted. Her habit quickly turned from buying pills, which were expensive on the street, to snorting and then injecting heroin, which came cheap and pure. Twelve years into their marriage, Brennan’s husband committed suicide. Then she lost her house. Brennan’s two older kids went to stay with her sister, and Brennan hasn’t seen them in over a year. “I’m a drug addict,” Brennan says bluntly. “She won’t give them back.”
Brennan started taking Suboxone, an opioid-replacement therapy that cut her cravings and kept her from experiencing withdrawal, two different times: in 2015 and then again from 2016 to 2018. During the second round, Brennan spent more than two years making trips to Prevention Point Philadelphia on Kensington Avenue. There, she met with her case manager and the doctor who prescribed her medication. Brennan seemed poised to be a success story. But she was weighed down by the stress of coping with a drug-addicted second husband, caring for her daughter Gemma, who is autistic; and despairing that she might never see her two older children again.
Copyright 2019 Undark

/ By Dave Levitan
Scientific research on the effects of marijuana is rife with holes, thanks in large part to it still being categorized at the federal level alongside drugs such as heroin and LSD. Unfortunately, when research is scarce, it becomes easier to mislead people through cherry-picked data, sneaky word choice, and misinterpreted conclusions.
On virtually every issue in his 272-page book, Adam Berenson commits one of the most common logical errors: He mixes up correlation and causation.
Which brings us to Alex Berenson and Malcolm Gladwell, and what happens when tidy narratives outrun the science.
Two weeks ago, Berenson, a former New York Times reporter and subsequent spy novelist, published a book with the ominous title “Tell Your Children: The Truth about Marijuana, Mental Illness, and Violence.” Gladwell, meanwhile, published a feature in the New Yorker, where he is a staff writer, drawing largely on Berenson’s book and questioning the supposed consensus that weed is among the safest drugs. Combined, these two works offer a master class in statistical malfeasance and a smorgasbord of logical fallacies and data-free fear-mongering that serve only to muddle an issue that, as experts point out, needs far more good-faith research.
Berenson’s main argument is relatively simple. In his book, he claims, essentially, that the existing evidence really does contain solid answers, painting a truly alarming picture about marijuana: That it can and does cause psychosis and schizophrenia. He then makes the leap that since psychosis and schizophrenia can lead to violence, marijuana itself is causing violence to increase in the United States and elsewhere.
Copyright 2019 Undark

By Diana Kwon o
For the longest time the cerebellum, a dense, fist-size formation located at the base of the brain, never got much respect from neuroscientists.
For about two centuries the scientific community believed the cerebellum (Latin for “little brain”), which contains approximately half of the brain’s neurons, was dedicated solely to the control of movement. In recent decades, however, the tide has started to turn, as researchers have revealed details of the structure’s role in cognition, emotional processing and social behavior.
The longstanding interest in the cerebellum can be seen in the work of French physiologist Marie Jean Pierre Flourens—(1794–1867). Flourens removed the cerebella of pigeons and found the birds became unbalanced, although they could still move. Based on these observations, he concluded the cerebellum was responsible for coordinating movements. “[This] set the dogma that the cerebellum was involved in motor coordination,” says Kamran Khodakhah, a neuroscientist at Albert Einstein College of Medicine, adding: “For many years, we ignored the signs that suggested it was involved in other things.”
One of the strongest pieces of evidence for the cerebellum’s broader repertoire emerged around two decades ago, when Jeremy Schmahmann, a neurologist at Massachusetts General Hospital, described cerebellar cognitive affective syndrome after discovering behavioral changes such as impairments in abstract reasoning and regulating emotion in individuals whose cerebella had been damaged. Since then this line of study has expanded. There has been human neuroimaging work showing the cerebellum is involved in cognitive processing and emotional control—and investigations in animals have revealed, among other things, that the structure is important for the normal development of social and cognitive capacities. Researchers have also linked altered cerebellar function to addiction, autism and schizophrenia.

A new study in rodents has shown that the brain’s cerebellum—known to play a role in motor coordination—also helps control the brain’s reward circuitry. Researchers found a direct neural connection from the cerebellum to the ventral tegmental area (VTA) of the brain, which is an area long known to been involved in reward processing and encoding. These findings, published in Science, demonstrate for the first time that the brain’s cerebellum plays a role in controlling reward and social preference behavior, and sheds new light on the brain circuits critical to the affective and social dysfunction seen across multiple psychiatric disorders. The research was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health.
“This type of research is fundamental to deepening our understanding of how brain circuit activity relates to mental illnesses,” said Joshua A. Gordon, M.D., Ph.D., director of NIMH. “Findings like the ones described in this paper help us learn more about how the brain works, a key first step on the path towards developing new treatments.”
The cerebellum plays a well-recognized role in the coordination and regulation of motor activity. However, research has also suggested that this brain area contributes to a host of non-motor functions. For example, abnormalities in the cerebellum have been linked to autism, schizophrenia, and substance use disorders, and brain activation in the cerebellum has been linked to motivation, social and emotional behaviors, and reward learning, each of which can be disrupted in psychiatric disorders.